Bottom Line:
Microglial cells are key players in the primary immune response of the central nervous system.They are highly active and motile cells that chemically and mechanically interact with their environment.Our results demonstrate that microglia are susceptible to mechanical signals, which could be important during central nervous system development and pathologies.

Affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge Cambridge, UK ; Faculty of Computer Science and Biomedical Engineering, Institute of Biomechanics, Graz University of Technology Graz, Austria.

ABSTRACTMicroglial cells are key players in the primary immune response of the central nervous system. They are highly active and motile cells that chemically and mechanically interact with their environment. While the impact of chemical signaling on microglia function has been studied in much detail, the current understanding of mechanical signaling is very limited. When cultured on compliant substrates, primary microglial cells adapted their spread area, morphology, and actin cytoskeleton to the stiffness of their environment. Traction force microscopy revealed that forces exerted by microglia increase with substrate stiffness until reaching a plateau at a shear modulus of ~5 kPa. When cultured on substrates incorporating stiffness gradients, microglia preferentially migrated toward stiffer regions, a process termed durotaxis. Lipopolysaccharide-induced immune-activation of microglia led to changes in traction forces, increased migration velocities and an amplification of durotaxis. We finally developed a mathematical model connecting traction forces with the durotactic behavior of migrating microglial cells. Our results demonstrate that microglia are susceptible to mechanical signals, which could be important during central nervous system development and pathologies. Stiffness gradients in tissue surrounding neural implants such as electrodes, for example, could mechanically attract microglial cells, thus facilitating foreign body reactions detrimental to electrode functioning.

Mentions:
Changes in cell spread area and in the F-actin cytoskeleton are often accompanied by changes in cellular forces (Tolic-Norrelykke and Wang, 2005; Califano and Reinhart-King, 2010; Fournier et al., 2010; Stricker et al., 2010). To measure microglial traction forces, we embedded fluorescent nanoparticles in compliant substrates, which allowed tracking substrate deformations due to forces exerted by cells (Figure 3).

Bottom Line:
Microglial cells are key players in the primary immune response of the central nervous system.They are highly active and motile cells that chemically and mechanically interact with their environment.Our results demonstrate that microglia are susceptible to mechanical signals, which could be important during central nervous system development and pathologies.

Affiliation:
Department of Physiology, Development and Neuroscience, University of Cambridge Cambridge, UK ; Faculty of Computer Science and Biomedical Engineering, Institute of Biomechanics, Graz University of Technology Graz, Austria.

ABSTRACTMicroglial cells are key players in the primary immune response of the central nervous system. They are highly active and motile cells that chemically and mechanically interact with their environment. While the impact of chemical signaling on microglia function has been studied in much detail, the current understanding of mechanical signaling is very limited. When cultured on compliant substrates, primary microglial cells adapted their spread area, morphology, and actin cytoskeleton to the stiffness of their environment. Traction force microscopy revealed that forces exerted by microglia increase with substrate stiffness until reaching a plateau at a shear modulus of ~5 kPa. When cultured on substrates incorporating stiffness gradients, microglia preferentially migrated toward stiffer regions, a process termed durotaxis. Lipopolysaccharide-induced immune-activation of microglia led to changes in traction forces, increased migration velocities and an amplification of durotaxis. We finally developed a mathematical model connecting traction forces with the durotactic behavior of migrating microglial cells. Our results demonstrate that microglia are susceptible to mechanical signals, which could be important during central nervous system development and pathologies. Stiffness gradients in tissue surrounding neural implants such as electrodes, for example, could mechanically attract microglial cells, thus facilitating foreign body reactions detrimental to electrode functioning.